New HIV drugs and treatment strategies look promising,
especially for people with resistant virus, and hepatitis C treatment has
entered a new era, researchers reported at the Conference on Retroviruses and
Opportunistic Infections this month in Atlanta.

As the pace of antiretroviral drug development has slowed, CROI
– now in its 20th year – has largely shifted its focus toward
treatment access, biomedical prevention, and related conditions such as
cardiovascular disease and hepatitis C.

There is also growing interest in research
that might one day lead to a functional cure for HIV, as demonstrated by the
biggest news out of Atlanta: a toddler in Mississippi who appears free of
active virus after starting antiretroviral therapy within two days of birth.

As antiretroviral drugs have become more effective, less
toxic, and easier to use, there is now more emphasis on the "cascade of
care" – the shrinking proportion of people with HIV at each successive
stage from testing to starting antiretroviral therapy to staying on treatment
and maintaining an undetectable viral load.

Looking at new HIV drugs presented at CROI, first out of the
pipeline is likely to be dolutegravir, ViiV Healthcare's next-generation
integrase inhibitor, which was submitted for Food and Drug Administration
approval late last year. New data from the
SAILING study show that dolutegravir worked better than
raltegravir (Isentress) – the sole approved drug in this class – for
treatment-experienced people with resistant HIV currently on failing therapy.

Andrew Zolopa from Stanford presented
findings from a study comparing Gilead Science's widely used TDF version of
tenofovir (Viread, also in
the Truvada, Atripla, Complera, and Stribild coformulations) to a new version
known as TAF. TAF reaches higher concentrations in cells than TDF, meaning it
can be used at much lower doses. People taking TAF in a new four-in-one
pill similar to Stribild had equivalent viral suppression and CD4 T-cell gains,
but less evidence of kidney dysfunction and bone loss.

Joseph Gathe from
Therapeutic Concepts in Houston reported
good results with Tobira
Therapeutics' dual-action cenicriviroc, which blocks both the CCR5 co-receptor
– one of the two gateways HIV
uses to enter cells – and the
CCR2 co-receptor, which plays a role in
inflammation. Further back in the pipeline, Merck
researchers presented promising early data on MK-1439, its next-generation
NNRTI.

Are NRTIs necessary?

People with highly resistant HIV – especially those
who started treatment with less effective therapy early in the epidemic –
may take multiple drugs in an effort to suppress the virus and make it less
"fit." But each additional
medication adds cost and side effects, leading Karen Tashima from Brown
University and colleagues to ask whether fewer might be better.

The ACTG OPTIONS trial enrolled 360 participants on failing
regimens with resistance to nucleoside/nucleotide analogs and NNRTIs. They had
been on treatment for 12 years on average and had a median CD4 count of only
200. Investigators put together optimized regimens, choosing among 20
combinations of potent modern drugs. Patients were then randomly assigned to
either add nucleosides/nucleotides or go nuke-free.

Omitting nucleoside/nucleotides worked just as well as
traditional regimens, with more than two-thirds of patients taking either
nuke-free or nuke-containing combinations achieving viral suppression within
one year. People in both groups had similar rates of side effect, but there
were significantly fewer deaths among the nuke-avoiders.

This study is a "game-changer," said Zolopa.
"Many of us are recycling nukes, but it looks quite convincing that we don't
have to do this."

Hepatitis C

Direct-acting antiviral drugs that target the hepatitis C
virus lifecycle – working much like HIV therapy – have ushered in a
new era of treatment. But the two drugs approved so far, Merck's boceprevir
(Victrelis) and Vertex's telaprevir (Incivek), must still be used with
pegylated interferon and ribavirin, and many patients and providers are waiting
for more tolerable therapy.

Anu Osinusi from the National Institutes of Health reported
results from the SPARE study, testing a simple two-drug combo of sofosbuvir plus
ribavirin for an inner-city population in Washington, D.C. Treatment was generally
well tolerated and cured 68 percent of participants taking the full standard
dose of ribavirin, but only 48 percent of those randomly assigned to a lower
ribavirin dose.

Sofosbuvir also looked good in a dual regimen with
Janssen/Medivir's once-daily HCV protease inhibitor simeprevir (TMC435). An
interim analysis of the COSMOS study, which looked at difficult-to-treat
genotype 1 prior null responders, showed that 92 percent treated for 12 weeks
and 100 percent treated for 24 weeks had undetectable HCV four weeks after
finishing treatment. This is too soon to declare a cure, but all 24
participants followed so far through post-treatment week 12 remain virus-free.

AbbVie (formerly Abbott) also saw some favorable data
showing that interferon-free regimens containing its once-daily HCV protease
inhibitor ABT-450, one of two HCV polymerase inhibitors (ABT-072 or ABT-333),
and ribavirin cured approximately 90 percent of previously untreated people,
though this fell to around half for prior non-responders.

HIV/HCV co-infection

CROI also offered good news for people with HIV/HCV co-infection.
Co-infected people experience more rapid liver disease progression and do not
respond as well to interferon, and many with advanced liver damage cannot wait
for interferon-free treatment.

Douglas Dieterich from Mt. Sinai School of Medicine
presented data showing that adding simeprevir to pegylated interferon and
ribavirin allowed many co-infected people to shorten treatment to 24 weeks and increased
the cure rate to 77 percent for treatment-naives and prior relapsers. Null
responders are still being followed, but so far two-thirds are still HCV-free.

Dieterich said the combined findings are "very
encouraging," with a consistent theme that HIV/HCV co-infected people have
outcomes about equal to those of patients with hepatitis C alone, although the
potential for interactions with antiretroviral drugs requires extra caution.

At a CROI news conference on hepatitis C research, experts
discussed what these mean for patients and providers. David Thomas from Johns
Hopkins predicted that the first components of interferon-free therapy will
likely be approved by the FDA by the end of the year. Comparing the hepatitis C
drug development timeline to HIV, he said, "It's as if we're going from
Crixivan to Atripla in a year and a half."

"It's like HIV drug development at warp speed,"
Dieterich concurred. "It's a really good time to have hep C."

Acute hepatitis C

Finally, Daniel Fierer, also from Mt. Sinai, looked at
treatment of HIV-positive gay and bisexual men with new sexually transmitted
HCV infection. Acute hepatitis C often has no symptoms, so most people do not
seek treatment when they first become infected. But HIV-positive people taking
antiretrovirals receive regular liver function tests, and unexpected elevations
can reveal recent HCV infection.

Interferon-based treatment is very effective for early HCV
infection, but less so for people with HIV. Fierer asked whether adding
telaprevir to pegylated interferon and ribavirin for 12 weeks could improve
response for HIV-positive men with newly acquired genotype 1 HCV. Interim findings
showed that 82 percent had undetectable HCV at 12 weeks after finishing
treatment.

While starting pegylated interferon and ribavirin during
acute HCV infection doubles the cure rate in half the time compared with
treatment during chronic infection, adding telaprevir is "twice as good"
and cuts treatment time in half again, Fierer said, suggesting that triple
therapy should be the new standard for acute hepatitis C.

"Don't wait for interferon-free," he urged,
because – as with HIV – treatment is prevention.